Non-invasive neuromodulation via targeted delivery of neurotransmitter chemicals

项目摘要： 博士Nicholas托德正在申请NIH指导研究科学家发展奖， 三个相互关联的目标：1）接受培训，获得神经科学两个关键领域的专业知识; 2）发展 基于神经递质靶向递送的非侵入性神经调节的新方法 化学物质的大脑; 3）建立一个坚实的基础，从启动作为一个独立的职业生涯 研究科学家赠款提案是为实现这些目标而量身定制的， 指导专业知识，培训计划和研究目标。 博士托德是一名磁共振成像（MRI）物理学家，他接受过磁共振成像（MR）方面的培训， 引导聚焦超声（FUS）应用和MR神经成像。他的抱负是要有一个长期的 作为一名独立的科学家，使用FUS和MRI的工具来进一步了解我们的研究生涯 大脑功能和神经系统疾病的先进治疗方法。为了完善他的技能， 这样的职业生涯，他现在正在寻求系统级神经科学的两个关键领域的培训， 大脑网络的神经生物学和分析神经成像数据的现代计算方法， 以及FUS介导的血脑屏障（BBB）开放的特定领域的专业知识。下 特殊的指导，博士托德将获得神经生物学的全面了解， 疼痛网络（主要导师，大卫博士Borsook），成为熟练应用动态因果关系 神经成像数据分析建模（导师Lino Becerra博士和合作者Karl Friston博士）， 并成为FUS介导的BBB开放的专家（导师Nathan McDannold博士）。 该提案中的研究目的是基于托德博士在MR神经成像和FUS方面的经验 在培训领域，他可以直接获得经验。研究工作将 开发和验证使用FUS的非侵入性神经调节新方法的方法， 介导的血脑屏障开放，将神经递质递送至靶向脑区域。目标 神经递质递送方法将用于研究啮齿动物疼痛网络的调节。 兴奋性（谷氨酸）和抑制性（GABA）神经递质将被传递到疼痛的节点 网络（丘脑和躯体感觉皮层）在健康和神经病理性疼痛大鼠。其影响将是 在整个疼痛网络中使用三种功能性方法进行测量， MRI（fMRI）、动态因果模型（DCM）和行为测试。 这项工作将推动托德博士沿着他的道路成为一个独立的科学家。培训 该组件将为托德博士提供系统级神经科学的必要知识， 职业生涯使用MRI和FUS进行大脑相关研究;研究部分将开发一个新的 非侵入性神经调节的方法，这将成为未来工作和资助申请的基础。

Project Summary: Dr. Nicholas Todd is applying for an NIH Mentored Research Scientist Development Award to achieve three interrelated goals: 1) undergo training to gain expertise in two key areas of neuroscience; 2) develop a novel approach to non-invasive neuromodulation based on targeted delivery of neurotransmitter chemicals to the brain; 3) build a strong foundation from which to launch a career as an independent research scientist. The grant proposal has been tailored to achieve these goals by aligning the mentorship expertise, training program, and research aims. Dr. Todd is a magnetic resonance imaging (MRI) physicist by training with particular experience in MR- guided focused ultrasound (FUS) applications and MR neuroimaging. His ambition is to have a long research career as an independent scientist using the tools of FUS and MRI to further our understanding of brain function and advance treatments for neurological diseases. In order to round out his skill set for such a career, he is now seeking training in two key areas of systems level neuroscience, the neurobiology of brain networks and modern computational methods for analyzing neuroimaging data, and also expertise in the specific area of FUS-mediated blood-brain barrier (BBB) opening. Under exceptional mentorship, Dr. Todd will gain a comprehensive understanding of the neurobiology of the pain network (primary mentor, Dr. David Borsook), become proficient in applying Dynamic Causal Modeling for analysis of neuroimaging data (mentor Dr. Lino Becerra and collaborator Dr. Karl Friston), and become an expert in FUS-mediated BBB opening (mentor Dr. Nathan McDannold). The research aims in the proposal build on Dr. Todd’s experience with MR neuroimaging and FUS applications, while providing him with direct experiences in the areas of training. The research work will develop and validate methodology for a novel approach to non-invasive neuromodulation that uses FUS- mediated BBB opening to deliver neurotransmitters to targeted brain regions. The targeted neurotransmitter delivery method will be used to investigate modulation of the rodent pain network. Excitatory (glutamate) and inhibitory (GABA) neurotransmitters will be delivered to nodes of the pain network (thalamus and somatosensory cortex) in healthy and neuropathic pain rats. The effects will be measured throughout the entire pain network using the three complimentary approaches of functional MRI (fMRI), Dynamic Causal Modeling (DCM), and behavioral testing. This work will advance Dr. Todd along his path towards becoming an independent scientist. The training component will provide Dr. Todd with the necessary knowledge of systems level neuroscience to pursue a career using MRI and FUS for brain related research; the research component will develop a new method for non-invasive neuromodulation that will form the basis of future work and grant applications.